The 12th Invest in ME Conference, Part 1
OverTheHills presents the first article in a series of three about the recent 12th Invest In ME international Conference (IIMEC12) in London.
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Dr. Edwards can you offer an opinion... polyclonal IgM

Discussion in 'General Treatment' started by Pyr2, Oct 15, 2015.

  1. Pyr2

    Pyr2

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    I have posted here before. I would love to know your take on those of us with actual polyclonal globulin increase and what it means for treatment.

    I have had long term, persistent EBV titers, over 30 yrs. All was well until a "flare" of nerve/pain related symptoms in 1999 which resolved on their own. The investigation from that revealed polyclonal IgM (usually in the 300 range) and a bone marrow cytogenetic result for del4(q21-35) that showed lymphoproliferative disease. The bone marrow itself and flow cytometry were normal and a bone marrow cytogenetic result for del4(q21-35) that showed lymphoproliferative disease. The bone marrow itself and flow cytometry were normal.

    I went without any physical symptoms for the next 12 years. However, through the years I developed a positive histone, ANA low (homogeneous), raynauds and anticardiolipin antibodies. But still in very good health and feeling well.

    Then, in 2013, the symptoms returned with a vengeance and never left. Lyme dr. says I have reactivated EBV and Lyme.

    I dont feel better after a year of treatment. Symptoms worsening.
    Rheumatologist says lots of autoimmune markers but you don't have autoimmune disease. You have chronic activation of your immune system. She is referring me to neurologist and immunologist. I already have an ID apptmt next week.

    Is this just a fancy way of saying I have CFS/ME? I have polyclonal IgM with normal levels of Kappa lambda but a high ratio (kappa 19.4) (lambda 9). (Ratio = 2.06 high).

    Would this qualify me for rituximab or some other treatment b/c I show actual evidence of a problem? Am I part of the Lerner subset? I did start Valcyte 7 weeks ago and feel like hell.

    I dont even know who to go to anymore. And the drs say that the lympoproliferative bone marrow cytogenetic was probably artifact but isn't ebv a b cell polyclonal?

    Im so confused! I feel like the possible bone marrow invovlement is very significant. Any ideas, thoughts, etc? They say no bone marrow involvement b/c I not tired, all cbc numbers are good, not anemic.

    Any wisdom you can shed, I would be SO grateful.
    L
     
  2. barbc56

    barbc56 Senior Member

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    @Pyr2

    If you use the above format with Jonathan Edward's name, he will get an alert that you have tagged him.

    Barb
     
  3. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    If you have a polyclonal rise in IgM and a shifted kappa/lamba ratio and at least the rheumatologist admits 'lots of autoimmune markers' then to my mind it is highly likely that you have a disturbance of B cell regulation and quite reasonable to think that it may be the cause of ME/CFS type symptoms. We know that people with ANA as part of Sjogren's or other syndromes bordering on lupus get fatigue that may well fall into the ME/CFS pattern.

    A lot of rheumatologists work on the basis that either you have disease X or disease Y or you don't have a disease. Since the antibody repertoire is unbelievably complicated I have always assumed that these 'diseases' are just the most common patterns and that there will be as many people, or more, who are ill but do not fit X or Y. I am not in a position to give you personal medical advice because I do not know all your details but in this sort of situation in my own clinic I would consider the problem in pragmatic terms - i.e. what seemed to make some sort of sense - without feeling I had to diagnose X or Y.

    I would personally forget about EBV and Lyme. Everyone has EBV. Whatever is wrong with your B cells it is not the presence of EBV but something wrong with the way they are regulated. If you have a polyclonal antibody rise then you may get high antibody results for all sorts of microbes and I cannot see why Lyme should have anything to do with this.

    When we studied the use of rituximab in RA we found that anyone with abnormally high levels of antibodies, of any sort, tended to respond. They did not have to have rheumatoid factors. All that seemed to indicate likely response was some clue that B cell regulation was wrong. So on that basis I suspect that people with ME/CFS with high levels of particular antibody classes may be more likely to respond to rituximab if indeed it does work. The problem at the moment is that we still are not sure on that.

    You may find an immunologist with a wide angle view on things who may give you a helpful explanation and even suggest some treatment. But to be fair to clinicians this is an area where it is often hard to give a firm explanation because we simply do not understand enough to be able to do that. At the moment using rituximab outside trials is not something I would recommend. I spoke to Dr Fluge on Tuesday and he is firmly of that opinion too.
     
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  4. Theodore

    Theodore Senior Member

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    Why is that Dr.?
     
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  5. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Partly because it is a very complicated drug to use safely and effectively and even in RA where it is licensed and there is a drug company based protocol a lot of physicians have been using it unwisely and getting unnecessary problems. I am afraid that physicians who offering rituximab outside trials are likely to be just the ones who do not understand how to use it.

    Partly because we just do not know if it has any effect yet.

    Partly because it does have some rare but very serious side effects.
     
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  6. Theodore

    Theodore Senior Member

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    I agree.

    The responding rate from the trials means there is an effect, isn't it?

    Ok.
     
  7. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    No, the 'responding rate' is based on selection of one particular time point rather than others. It may be a fluke of random fluctuation in patients' symptoms. There were large fluctuations in symptom levels in both treated and control patients over time. It may just be by luck that a t six months the treated patients all happened to be having a good patch - at three months they were not.
     
  8. Theodore

    Theodore Senior Member

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    You mean it happened for other ME treatments?
     
  9. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Not sure what you mean there.
     
  10. Theodore

    Theodore Senior Member

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    You said
    In which trials there were large fluctuation? In ME related trials?
     
  11. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    In the phase 2 ME rituximab trial.
     
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  12. sillysocks84

    sillysocks84 Senior Member

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    So since they know what rtx is doing to get good outcomes in a significant subset, could they find something that will do the same without the side effects? Are they looking at other ways?
     
  13. Pyr2

    Pyr2

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    Thanks Dr. E. Most doctors say try and find the cause of your polyclonal gammopathy to get rid of the symptoms, but my doctors have looked exhaustingly and nothing is coming up. I mean we are down in the weeds. Just the reactviated EBV and LYme titers to specific bands (39, 23, etc). My symptoms are horrible cranial neuralgias and all over nerve signals gone wrong, eye muscle pulling, twitching, brow drooping. It feels critical to me like Im a month away from total body nerve breakdown/paralysis. I have been on a quest to identify the PG so that I can get treated. I am almost hoping for a bad EMG next week that shows something they can potentially treat with something, anything- IVIG, plasmapherosis, etc.

    You said forget about the ebv and the lyme. I don't want to belabor this, but what do you mean? Isn't it possible that my disregulating immune system can't contain them and thus what I am experiencing are breakthrough symptoms from those diseases - for example, most of my symptoms are classic for neuro lyme. And what does that mean for the valcyte then, useless in the face of immune dysfunction?
     
  14. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    I think you should get some fresh medical opinions, as you are planning. I am not sure that I can say more than I have already said without knowing all your details. In general terms I think it more likely that a polyclonal gammopathy may give rise to false positive Lyme testing than that there be actually any relation to Lyme infection.
     
  15. Pyr2

    Pyr2

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    Thank you so much for your opinion!
     

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